Chemoprevention of Colorectal Cancer by Dietary Compounds

Abstract

Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds' bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.

Keywords: chemoprevention; colorectal cancer; dietary compounds.

Figure 1

Schematic representation of the polyphenols’ major mechanisms of action on colorectal cancer (CRC) cells. Polyphenols: (i) Determine cell cycle arrest by downregulating cyclin-dependent kinase 2, 4 (CDK 2, 4), (ii) induce apoptosis by upregulating B cell lymphoma 2 associated protein X and B cell lymphoma 2 (Bax-Bcl-2), caspase-3 and caspase-8, (iii) inhibit cell adhesion and migration through the downregulation of matrix metalloproteinase 9 (MMP-9) and cyclooxygenase 2 (COX2) and (iv) stop tumor initiation by altering nuclear factor kappa-light-chain-enhancer of B cells (NF-kb)/β-catenin signaling pathway.

Figure 2

Schematic representation of the non-polyphenolic compounds’ major mechanisms of action on CRC cells. Non-polyphenolic compounds: (i) Determine cell cycle arrest by downregulating cyclin-dependent kinase 1 (CDK 1), (ii) induce apoptosis by upregulating B cell lymphoma 2 associated protein X (Bax), B cell lymphoma 2 (Blc-2) and by increasing the production of reactive oxygen species (ROS), (iii) exert anti-inflammatory effects by downregulating interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6) and cyclooxygenase 2 (COX2), (iv) inhibit angiogenesis and invasion by downregulating matrix metalloproteinase 7 (MMP-7) and phosphoinositide 3-kinase (PKI3)/Protein kinase B (Akt) and (v) stop tumor initiation by altering the PKI3/Akt pathway.